TY - JOUR
T1 - Selective cell death of p53-insufficient cancer cells is induced by knockdown of the mRNA export molecule GANP
AU - Phimsen, Suchada
AU - Kuwahara, Kazuhiko
AU - Nakaya, Teruo
AU - Ohta, Kazutaka
AU - Suda, Taiji
AU - Rezano, Andri
AU - Kitabatake, Masahiro
AU - Vaeteewoottacharn, Kulthida
AU - Okada, Seiji
AU - Tone, Shigenobu
AU - Sakaguchi, Nobuo
N1 - Funding Information:
Acknowledgments We would like to thank Mika Ito and Yoshimi Fukushima for technical assistance. This work was supported by a Grant-in-Aid for Science Research in a Priority Area (Immunology Community) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to N.S.), Advanced Education Program for Integrated Clinical, Basic and Social Medicine, Graduate School of Medical Sciences, Kumamoto University (Program for Enhancing Systematic Education in Graduate Schools, MEXT) (to N.S.), the Adaptable and Seamless Technology Transfer Program through Target-driven R&D (Japan Science and Technology Agency) (to K.K.), Heiwa Nakajima Foundation (to S.O., K.V., and K.K.), a contract research fund from the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases (to N.S.), and a Global COE program (Global Education and Research Center Aiming at the control of AIDS in Kumamoto University) (to N.S.). Suchada Phimsen is supported by a scholarship for The International Priority Graduate Programs (PGP); Advanced Graduate Courses for International Students (Doctoral Course), MEXT, Japan.
PY - 2012/7
Y1 - 2012/7
N2 - Cancer cells often contain p53 abnormalities that impair cell-cycle checkpoint progression and cause resistance to various anti-cancer treatments. DNA damage occurs at actively transcribed genes during G1-phase in yeast cells that have a deficient mRNA export capacity. Here, we show that germinal center-associated nuclear protein (GANP), a homologue of yeast Sac3 that is involved in mRNA export, is indispensable for ensuring the stability of human genomic DNA and that GANP knockdown causes apoptosis and necrosis of p53-insufficient cancer cells. Ganp small interfering RNA (siGanp)-induced DNA damage, accompanied by a decrease in the number of cells in S-phase, caused late apoptosis and necrosis in p53-insufficient cancer cells through both caspase-dependent and -independent mechanisms. siGanp effectively induced DNA damage leading to cell death in p53-insufficient cancer cells in vitro and protect the growth of cancer cells transplanted into immunocompromized mice, suggesting that siGanp has potential as a selective treatment for p53-insufficient cancer cells.
AB - Cancer cells often contain p53 abnormalities that impair cell-cycle checkpoint progression and cause resistance to various anti-cancer treatments. DNA damage occurs at actively transcribed genes during G1-phase in yeast cells that have a deficient mRNA export capacity. Here, we show that germinal center-associated nuclear protein (GANP), a homologue of yeast Sac3 that is involved in mRNA export, is indispensable for ensuring the stability of human genomic DNA and that GANP knockdown causes apoptosis and necrosis of p53-insufficient cancer cells. Ganp small interfering RNA (siGanp)-induced DNA damage, accompanied by a decrease in the number of cells in S-phase, caused late apoptosis and necrosis in p53-insufficient cancer cells through both caspase-dependent and -independent mechanisms. siGanp effectively induced DNA damage leading to cell death in p53-insufficient cancer cells in vitro and protect the growth of cancer cells transplanted into immunocompromized mice, suggesting that siGanp has potential as a selective treatment for p53-insufficient cancer cells.
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U2 - 10.1007/s10495-012-0711-8
DO - 10.1007/s10495-012-0711-8
M3 - Article
C2 - 22395445
AN - SCOPUS:84862496690
VL - 17
SP - 679
EP - 690
JO - Apoptosis : an international journal on programmed cell death
JF - Apoptosis : an international journal on programmed cell death
SN - 1360-8185
IS - 7
ER -